1100delC

1100delC refers to a specific genetic variant in the CHEK2 gene, designated c.1100delC. It is a deletion of a cytosine at nucleotide position 1100, causing a frameshift and a premature stop codon. The result is a truncated, nonfunctional CHEK2 protein, leading to impaired DNA damage signaling and cell cycle control.

The mutation is best known as a founder variant in Northern and Eastern European populations, with the highest frequencies reported in the Dutch population and among people of nearby ancestry. Carriers of 1100delC have a moderately increased risk of breast cancer compared with non-carriers, with estimates commonly described as approximately two- to three-fold higher, though exact risk varies with family history and other factors. Some studies have suggested associations with increased risk for colorectal cancer and possibly other cancers, but findings are less consistent and not as well established.

Clinical implications center on risk assessment rather than definitive prediction of cancer. CHEK2 1100delC testing is included in some hereditary cancer panels, particularly for individuals with a family history of breast or related cancers. In carriers, management typically relies on individualized risk assessment and established screening guidelines, rather than population-wide prevention strategies. Counseling emphasizes understanding that the risk is modest in comparison with high-penetrance BRCA1 or BRCA2 mutations.

Functionally, CHEK2 encodes a serine/threonine kinase that participates in the DNA damage response, promoting cell cycle arrest and repair through pathways involving p53 and BRCA1. Loss of CHEK2 function can contribute to genomic instability and elevated cancer risk.